5-HT2A receptor/protein kinase C pathway in mediating long-term facilitation of carotid sinus nerve discharge in chronic intermittent hypoxia rats
- Author:
- No author available
- Journal Title:
- Chinese Journal of Tuberculosis and Respiratory Diseases
- Issue:
- 8
- DOI:
- 10.3760/cma.j.issn.1001-0939.2018.08.008
- Key Word:
- 5-羟色胺2A受体;蛋白激酶C;慢性间歇低氧;颈动脉体窦神经;长时程易化;5-HT2AR;Protein kinase C;Chronic intermittent hypoxia;Carotid sinus nerve;Long-term facilitation
Abstract： Objective To explore the role of 5-HT2A R/PKC pathway in mediating long-term facilitation (LTF) of carotid sinus nerve (CSN) discharge in chronic intermittent hypoxia (CIH) rats.Methods With number table,24 adult SD rats were randomly divided into saline control group (group A,n =6),5-HT2AR antagonist (ketanserin) group (group B,n =6),PKC inhibitor (PKC θ-pseudosubstrate)group (group C,n =6) and combined ketanserin with PKC θ-pseudosubstrate group (group D,n =6).All rats were placed into the animal chambers for CIH treatment,8 h per day (from 9:00 to 17:00) for 4 consecutive weeks.28 days later,5 min × 3 times of stimulation with acute intermittent bypoxia (AIH)were given,after that,stable CSN discharge activities were recorded and compared before and after intravenous injection of saline (group A),ketanserin (group B),PKC θ-pseudosubstrate (group C) or ketanserin + PKC θ-pseudosubstrate (group D),respectively.Results There were no significant difference in the baseline (before AIH stimulation) average peak amplitude of CSN discharge among the four groups (P ＞ 0.05).In group A,the amplitude of CSN discharge at 30 min and 60 min after AIH were (5.01 ± 0.53) μV and (4.95 ± 0.34) μV respectively,which were significantly higher than that before AIH (P ＜0.01).The results implied that the CSN LTF could be induced by AIH in CIH pre-treatment rats.In group B,the amplitude of CSN discharge at 30 min and 60 min after AIH were (3.79 ± 0.42) μV and (3.73 ± 0.46) μV,respectively,which were still significantly higher than that before AIH (P ＜0.01),showing that carotid sinus nerve LTF couldn't be completely blocked by 5-HT2AR antagonist in rats.After injection of PKC θ-pseudosubstrate or ketanserin + PKC θ-pseudosubstrate in group C or D,there were no significant differences in CSN discharge amplitude before and after AIH (P ＞0.01),suggesting that inhibition of PKC alone or 5-HT2AR/PKC pathway could completely block the LTF of CSN.Conclusion 5-HT2AR/PKCpathway was involved in mediating long-term facilitation of carotid sinus nerve discharge in CIH rats.
- [1]康晶,赵景景,胡克.间歇低氧诱导呼吸长时程易化与阻塞性睡眠呼吸暂停低通气综合征关系的研究进展[J].2011,(12).
- [2]兰星,余晓曼,胡克,等.不同剂量5-羟色胺受体配体对慢性间歇低氧大鼠颏舌肌长时程易化的影响[J].2015,(6).
- [3]N R, Prabhakar.Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms.[J].2001,90(5).
- [4]Yuan G,Prabhakar NR,Nanduri J,etc.NADPH oxidase is required for the sensory plasticity of the carotid body by chronic intermittent hypoxia.[J].2009,29(15).
- [5]Maurice, Dematteis,Diane, Godin-Ribuot,Claire, Arnaud,etc.Cardiovascular consequences of sleep-disordered breathing: contribution of animal models to understanding the human disease.[J].2009,50(3).
- [6]Peng YJ,Overholt JL,Kline D,etc.Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: Implications for recurrent apneas.[J].2003,100(17).
- [7]W T, McNicholas,M R, Bonsigore,M R, Bonsignore.Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities.[J].2007,29(1).
- [8]Yingjie, Peng,Guoxiang, Yuan,Jeffrey L, Overholt,etc.Systemic and cellular responses to intermittent hypoxia: evidence for oxidative stress and mitochondrial dysfunction.[J].2003,536.
- [9]Saywell SA,Feldman JL,Neverova NV.Modulation of hypoglossal motoneuron excitability by intracellular signal transduction cascades.[J].2005,147(2).
- [10]Svatikova A,Olson LJ,Wolk.Obstructive sleep apnea and aldosterone.[J].2009,32(12).
- [11]D D, Fuller,A G, Zabka,T L, Baker,etc.Phrenic long-term facilitation requires 5-HT receptor activation during but not following episodic hypoxia.[J].2001,90.
- [12]Peng YJ,Jacono FJ,Kumar GK,etc.5-HT evokes sensory long-term facilitation of rodent carotid body via activation of NADPH oxidase.[J].2006,576(Pt.1).